AUTHOR=Li Dan , Zhu Yue , Song Jincheng , Yang Dafu , Cui Saiqiong , Liu Xin , Wang Le , Zhang Jiangyan , Pan Evenki , Dai Zhaoxia 

TITLE=Rapid response to fifth-line brigatinib plus entrectinib in an ALK-rearranged lung adenocarcinoma with an acquired ETV6-NTRK3 fusion: a case report

JOURNAL=Frontiers in Oncology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1339511

DOI=10.3389/fonc.2024.1339511

ISSN=2234-943X

ABSTRACT=<p>The management of non-small cell lung cancer (NSCLC), specifically targeting the anaplastic lymphoma kinase (<italic>ALK</italic>) with tyrosine kinase inhibitors (TKIs), is challenged by the emergence of therapeutic resistance. Resistance mechanisms to <italic>ALK</italic> TKIs can be broadly classified into ALK-dependent and ALK-independent pathways. Here, we present a case with lung adenocarcinoma (LUAD) harboring an <italic>ALK</italic> rearrangement. The patient had developed resistance to sequential ALK TKI therapies, with an acquired <italic>ETV6-NTRK3</italic> (E4:N14) fusion as a potential mechanism of <italic>ALK</italic>-independent resistance to lorlatinib. Subsequently, the patient was treated with the combination of brigatinib plus entrectinib and demonstrated a positive response, achieving an 8-month progression-free survival. Our case provides a potential treatment option for LUAD patients with <italic>ALK</italic> rearrangements and highlights the utility of next-generation sequencing (NGS) in uncovering genetic alterations that can guide the selection of effective treatment strategies.</p>